COMMENT:DES: MAKING AMENDS

A generation ago, doctors all over the world handed out a drug to women that they said would prevent miscarriage. No one thought to ask how this drug might effect the resulting children. Only now, as this generation themselves struggle to have childr

The drug, known as diethylstilbestrol (DES), more commonly stilbestrol in the UK, has been known to cause a rare vaginal cancer since 1971. More recently, prenatal exposure to DES has been found to cause benign changes of the genital tract in both daughters and sons, which can lead to problems with fertility and pregnancy. DES hormonal exposure may be one of the factors behind the huge surge of infertility we are experiencing today.

DES is a synthetic estrogen hormone first developed in 1938. It is three times more potent that the natural estrogen, estradiol. Stilbestrol’s main use was aimed at women with a history of miscarriage, spotting and bleeding during a pregnancy, or those suffering from diabetes. It was prescribed in early fetal development, usually for the full pregnancy.

DES was given to millions of women worldwide. However, lack of cooperation from the pharmaceutical industry in providing sales records and a lack of cancer registers in many countries make it difficult to estimate true DES exposure. If DES had been prescribed throughout Europe at the same rate as the US, between 4.5 and 9 million European people would have been exposed in utero.

As early as 1953 medicine realized that DES had little effect in preventing miscarriages. Nevertheless, doctors continued to prescribe it until 1971, when in the US DES was found to be linked with clear-cell adenocarcinoma of the vagina and/or cervix in exposed daughters This type of cancer had almost never appeared in young women prior to the menopause. After DES, however, clusters of young women were showing up with this cancer, mainly at puberty or in their early 20s or 30s.

Warnings were immediately sent out to doctors and drug companies. Although its use declined rapidly in the US, these warnings did not appear in the UK until 1973. DES continued to be prescribed until as late as 1978 in the UK and 1981 in Europe.

Cancer from DES is rare, developing in between one in 1000 and one

in 10,000 children exposed pre-natally. Dysplasia is an abnormal structure of the tissue covering the cervix, considered to be potentially malignant. DES daughters have double the incidence (15 per cent) of non-exposed women. This abnormal tissue is classified in four grades. The first two require vigilance more than treatment, as they may disappear spontaneously. But once it does develop, this cancer is particularly fast-growing and invasive, requiring radical mutilating surgery, including vaginectomies, hysterectomies and further extensive surgery to bladder and bowel.

Perhaps more insidious (because less is known about it), DES exposed women have a number of lower genital tract anomalies, which can be seen with the naked eye (if a doctor knows to look). These include underdeveloped cervixes and, most characteristically, a cockscomb cervix (a deformity of the anterior cervical lip, giving it a peaked appearance). An underdeveloped cervix may cause inadequate cervical function during pregnancy. Furthermore, 40 to 60 per cent of DES exposed daughters have pronounced uterine structural abnormalities.

Infertility has been reported in about one-third of cases (Ob Gyn, 1980; 56: 333-5, Ob Gyn, 1980; 96: 275-80, Ob Gyn, 1982; 59: 685-725) and twice as often in the exposed group than among the unexposed (Am J Ob Gyne, 1988; 158: 493-8).

More than four to eight times as many of the DES exposed have tubal pregnancies than the unexposed. A quarter of all pregnancies among the DES exposed miscarry compared with a normal 10 per cent rate.

Premature birth occurs in three times as many babies (15 per cent) of the DES exposed as those of the non-exposed. With DES induced gross abnormalities that risk can soar to 71 per cent.

As for DES exposed sons, nearly a third have testicular abnormalities, which increase male infertility. These include undescended testes, sperm abnormalities and low sperm counts. There is also the possibility of testicular cancer.

As yet, DES exposure and its link with infertility and pregnancy problems are not widely known, among infertility clinics, gynecological and maternity units.

As a matter of course, all women should be asked routinely if their mothers suffered from miscarriages and/or bleeding during pregnancy and if their mothers took any tablets while pregnant. This should also be recorded in their notes.

Those found to be DES exposed should also undergo an annual vaginal examination by trained doctors and nurses, to detect any changes in in what are already abnormal organs and tissue. Doctors doing the examining must know that abnormal cells can be present outside the normal area of the uterus and vaginal cancer even develop where these cells have been (but no longer are).

DES exposed women also need full information about the special higher risks of various contraceptives such as IUDs or the Pill.

Medicine made a drastic mistake with DES. Now it is up to medicine to develop a medical speciality to treat the illness and suffering it has caused. Only then will this generation of DES sons and daughters have a hope of producing another generation and have some restitution for the sins wreaked upon their mothers.